Unknown

Dataset Information

0

The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model.


ABSTRACT: The endoplasmic reticulum (ER) has a major role in protein folding. The accumulation of unfolded proteins in the ER induces a stress, which can be resolved by the unfolded protein response (UPR). Chronicity of ER stress leads to UPR-induced apoptosis and in turn to an unbalance of tissue homeostasis. Although ER stress-dependent apoptosis is observed in a great number of devastating human diseases, how cells activate apoptosis and promote tissue homeostasis after chronic ER stress remains poorly understood. Here, using the Drosophila wing imaginal disc as a model system, we validated that Presenilin overexpression induces chronic ER stress in vivo. We observed, in this novel model of chronic ER-stress, a PERK/ATF4-dependent apoptosis requiring downregulation of the antiapoptotic diap1 gene. PERK/ATF4 also activated the JNK pathway through Rac1 and Slpr activation in apoptotic cells, leading to the expression of Dilp8. This insulin-like peptide caused a developmental delay, which partially allowed the replacement of apoptotic cells. Thanks to a novel chronic ER stress model, these results establish a new pathway that both participates in tissue homeostasis and triggers apoptosis through an original regulation.

SUBMITTER: Demay Y 

PROVIDER: S-EPMC4649510 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model.

Demay Y Y   Perochon J J   Szuplewski S S   Mignotte B B   Gaumer S S  

Cell death & disease 20141009


The endoplasmic reticulum (ER) has a major role in protein folding. The accumulation of unfolded proteins in the ER induces a stress, which can be resolved by the unfolded protein response (UPR). Chronicity of ER stress leads to UPR-induced apoptosis and in turn to an unbalance of tissue homeostasis. Although ER stress-dependent apoptosis is observed in a great number of devastating human diseases, how cells activate apoptosis and promote tissue homeostasis after chronic ER stress remains poorly  ...[more]

Similar Datasets

| S-EPMC5857997 | biostudies-literature
| S-EPMC5533947 | biostudies-literature
| S-EPMC7932925 | biostudies-literature
| S-EPMC126061 | biostudies-literature
| S-EPMC4615047 | biostudies-literature
| S-EPMC3119309 | biostudies-literature
| S-EPMC4422665 | biostudies-literature
| S-EPMC6416471 | biostudies-literature
| S-EPMC6715248 | biostudies-literature
| S-EPMC7592913 | biostudies-literature